The effects of hyperthermia and irradiation seperately and combined are studied on lysosomes and lysosomal enzyme activity of cultured Hela cells and of mouse mammary tumors, both spontaneous and transplanted. Quantitative cytochemical and histochemical methods are used for all investigations of lysosomal enzymes and these are combined with electron microscopic studies of lysosomes. Effects of lysosomal labilizers, stabilizers, and radiosensitizers are used to ascertain the extent to which these can modify the effects of hyperthermia and irradiation on lysosomal enzyme activity. The objective of the investigation is to attempt to ascertain the roles played by lysosomes and lysosomal enzymes in tumor regression following treatment with irradiation or hyperthermia.